The overall goal of this proposal is to investigate the cellular and molecular mechanisms underlying pulsatile gonadotropin-releasing hormone (GnRH) secretion. GnRH neurons provide the final common pathway for the central neural control of reproduction in vertebrates. Release of GnRH in a rhythmic manner is absolutely essential for reproductive function and thus, an understanding of the control of GnRH release is not just of general biologic interest, but has broad clinical relevance with respect to the advancement and reversible suppression of fertility. Two complementary systems (GT1 cells and primary GnRH neurons) will be used to address the central goal. Specific Aim I is devoted to further development of methodologies. Specific Aim II will investigate the cellular location of the GnRH oscillator, addressing the hypothesis that individual neurons are biological oscillators by using electrical recording and calcium imaging techniques on single cells and populations of cells. Specific Aim III will investigate the biochemical nature of the oscillator, to address the hypothesis that the oscillator is metabolic in nature, by examining transcription, translation and kinase/phosphatase systems. Specific Aim IV will examine the mechanisms coordinating GnRH release, addressing the hypothesis that GnRH serves as a neuromediator coordinating its own release.